Previous work from this laboratory has been directed at the vascular adjustments to heart failure. This proposal extends that work. We now plan to examine the biochemical mechanisms for neurogenic, and humoral control of the heart and peripheral circulation in experimental right ventricular hypertrophy and failure and left ventricular hypertrophy and failure. Previous work supports the notion that compensatory mechanisms vary qualitatively in these situations. This will be explored further using three experimental models produced in guinea pigs by constricting either the pulmonary artery, the ascending aorta, or the descending thoracic aorta. We will examine biochemical indices of preganglionic and postganglionic function in regional sympathetic ganglia using choline acetyltransferase activity and tyrosine hydroxylase activity, respectively. Also, we will examine the biochemical indices of sympathetic function in regional tissues using the content and turnover of norepinephrine and the activity of tyrosine hydroxylase. Using these indices, we intend to study the regional pattern of neural adjustments to hypertrophy and heart failure, the biochemical mechanisms for altered neural control, and the variations in neural mechanisms associated with different types of hypertrophy and heart failure. We will investigate further the factors that contrubute to the regulation of vascular resistance in right and left ventricular hypertrophy and failure. Studies are planned to investigate whether catecholamines, angiotensin II, vasopressin, or another as yet unidentified hormone is responsible for the maintenance of vascular resistance. Studies are also planned to investigate the cause of altered vascular reactivity that was detected in the earlier studies of these models. The overall objective is to explore new leads and to deal with new specific questions that have evolved from our earlier studies of circulatory regulation in cardiac hypertrophy and failure.